Summary of findings 1. Metformin compared to oral contraceptive pill (OCP) for hirsutism, acne, and menstrual pattern in adult women with polycystic ovary syndrome (PCOS).
| Metformin compared to OCP for hirsutism, acne, and menstrual pattern in adult women with PCOS | |||||||
| Patient or population: adult women with PCOS Setting: Hospital or University Clinics Intervention: metformin Comparison: OCP | |||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Quality of the evidence (GRADE) | Comments | ||
| Risk with OCP | Risk with metformin | ||||||
| Hirsutism ‐ Clinical F‐G score | BMI ≤ 25kg/m2 | The mean hirsutism ‐ Clinical F‐G score was 7.5 | MD 0.38 higher (0.44 lower to 1.19 higher) | ‐ | 134 (3 RCTs) | ⊕⊝⊝⊝ VERY LOW1,2,3 | |
| BMI > 25 kg/m2 < 30 kg/m2 | The mean hirsutism ‐ Clinical F‐G score was 6.44 | MD 1.92 higher (1.21 higher to 2.64 higher) | ‐ | 254 (5 RCTs) | ⊕⊕⊝⊝ LOW1,4 |
||
| BMI ≥ 30 kg/m2 | The mean hirsutism ‐ Clinical F‐G score was 6.05 | MD 0.38 lower (1.93 lower to 1.17 higher) | ‐ | 85 (2 RCTs) | ⊕⊕⊝⊝ LOW1,5 |
||
| Adverse events ‐ Severe | Gastro‐intestinal | 3 per 1 000 | 21 per 1 000 (10 to 45) | OR 6.42 (2.98 to 13.84) | 602 (11 RCTs) | ⊕⊕⊝⊝ LOW 6,7 | |
| Others | 122 per 1000 | 27 per 1000 (12 to 57) |
OR 0.20 (0.09 to 0.44) | 363 (8 RCTs) | ⊕⊕⊝⊝ LOW 6,7 | ||
| Adverse events ‐ Minor | Gastro‐intestinal | No trials reported on outcome "Adverse events ‐ Minor ‐ Gastro‐intestinal" | |||||
| Others | No trials reported on outcome "Adverse events ‐ Minor ‐ Others" | ||||||
| Improved menstrual pattern | Shortening of intermenstrual days | The mean improved menstrual pattern (ie. shortening of intermenstrual days) was 32.4 | MD 6.05 higher (2.37 higher to 9.74 higher) | ‐ | 153 (2 RCTs) | ⊕⊕⊝⊝⊝ LOW 4,8 | |
| An initiation of menses or cycle regularity) ‐ ≤ 25 kg/m2 | 1000 per 1 000 | 1000 per 1 000 (1000 to 1000) | OR 0.07 (0.01 to 0.65) | 17 (1 RCT) | ⊕⊕⊝⊝ LOW 6,7 | ||
| An initiation of menses or cycle regularity)‐ BMI > 25 kg/m2 < 30 kg/m2 | 931 per 1000 | 669 per 1000 (486 to 817) | OR 0.15 (0.07 to 0.33) | 129 (3 RCTs) | ⊕⊝⊝⊝ VERY LOW 7,8,9 |
||
| An initiation of menses or cycle regularity) ‐ BMI ≥ 30 kg/m2 | 1000 per 1 000 | 1000 per 1 000 (1000 to 1000) | OR 0.09 (0.01 to 1.62) | 18 (1 RCT) | ⊕⊝⊝⊝ VERY LOW 6,10 | ||
| An initiation of menses or cycle regularity) ‐ BMI not stated | 500 per 1000 | 661 per 1000 (281 to 906) | OR 1.95 (0.39 to 9.65) | 25 (1 RCT) | ⊕⊝⊝⊝ VERY LOW 8,10 |
||
| Acne ‐ Visual analogue scale | The mean acne ‐ Visual analogue scale was 1 | MD 0.90 higher (0.40 lower to 2.20 higher) | ‐ | 34 (1 RCT) | ⊕⊕⊝⊝ LOW 11 | ||
| BMI (kg/m2) | BMI ≤ 25 kg/m2 | The mean BMI (kg/m2) was 22.7 | MD 0.59 lower (1.02 lower to 0.17 lower) | ‐ | 451 (9 RCTs) | ⊕⊝⊝⊝ VERY LOW 1,12,13 |
|
| BMI > 25 kg/m2 < 30 kg/m2 | The mean BMI (kg/m2) was 27.4 | MD 0.11 higher (0.48 lower to 0.7 higher) | ‐ | 353 (8 RCTs) | ⊕⊝⊝⊝ VERY LOW 1,14,15 |
||
| BMI ≥ 30 kg/m2 | The mean BMI (kg/m2) was 35.1 | MD 2.31 lower (4.40 lower to 0.21 lower) | ‐ | 119 (3 RCTs) | ⊕⊝⊝⊝ VERY LOW 1, 15,16 |
||
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). BMI: body mass index; CI: Confidence interval; F‐G: Ferriman‐Gallwey score; MD: Mean difference; OR: Odds ratio; RCT: Randomised controlled trial. | |||||||
| GRADE Working Group grades of evidence High quality: further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: we are very uncertain about the estimate. | |||||||
1 Evidence downgraded by one level for serious risk of bias ‐ the majority of the RCTs have unclear or high risk of bias 2 Evidence downgraded by one level for serious inconsistency (I2 = 50%) as unexplained heterogeneity (i.e. heterogeneity not explained by subgrouping of data according to mean study BMI)
3 Evidence downgraded by one level for serious imprecision – 95% CI includes both appreciable effect and little or no effect and low number of participants (total number of participants < 400)
4 Evidence downgraded by one level for serious imprecision – low number of participants (total number of participants < 400)
5 Evidence downgraded by one level for serious imprecision ‐ low number of participants (total number of participants < 400) and 95% CI includes both appreciable benefit and harm
6 Evidence downgraded by one level for serious risk of bias ‐ the majority of the RCTs have unclear risk of bias
7 Evidence downgraded by one level for serious imprecision – low number of events (total number of events < 300)
8 Evidence downgraded by one level for serious risk of bias ‐ the majority of the RCTs have high risk of bias
9 Evidence downgraded by one level for serious inconsistency (I2 = 51%) as unexplained heterogeneity (i.e. heterogeneity not explained by subgrouping of data according to mean study BMI)
10 Evidence downgraded by two levels for very serious imprecision – 95% CI includes both appreciable benefit and harm or no effect and very low number of events (total number of events < 300)
11 Evidence downgraded by two levels for serious imprecision – 95% CI includes both appreciable benefit and harm or no effect and low number of participants (total number of participants < 400)
12 Evidence downgraded by one level for serious inconsistency (I2 = 76%) as unexplained heterogeneity (i.e. heterogeneity not explained by subgrouping of data according to mean study BMI)
13 Evidence downgraded by one level for serious imprecision – 95% CI includes both appreciable effect and little or no effect
14 Evidence downgraded by one level for serious inconsistency (I2 = 72%) as unexplained heterogeneity (i.e. heterogeneity not explained by subgrouping of data according to mean study BMI)
15 Evidence downgraded by one level for serious imprecision ‐ low number of participants (total number of participants < 400) and 95% CI includes both appreciable effect and little or no effect
16 Evidence downgraded by one level for serious inconsistency (I2 = 52%) as unexplained heterogeneity (i.e. heterogeneity not explained by subgrouping of data according to mean study BMI)